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Biomedical subjects

J Yodoi

Publications and source records attributed to J Yodoi.

At least 127 records · Page 7Linked to original sources
PubMed1996

Protection against reperfusion-induced arrhythmias by human thioredoxin.

Adult T-cell leukemia-derived factor (ADF), identified in the supernatant of adult T-cell leukemia (ATL) cell culture, is a human homologue of thioredoxin and consists of 104 amino acids; it has two redox-active half-cysteine residues in an exposed active center. Human thioredoxin has many biological activities, including growth promotion, cell activation, and a catalase-like radical scavenging activity. We examined the protective effect of human thioredoxin (h-thioredoxin) against reperfusion-induced arrhythmias in an isolated rat heart model with 10-min regional ischemia followed by 30-min reperfusion. Male Wistar rats were assigned to six groups: a control, a superoxide dismutase (SOD 8 x 10(4) IU/L), and a catalase group (1 x 10(6) IU/L), and three groups treated with h-thioredoxin [approximately .01 microM (TRX-I group), approximately 0.1 microM (TRX-II group), and approximately 1 microM (TRX-III group)]. In the early reperfusion period, h-thioredoxin reduced the incidence of ventricular fibrillation (VF) to 8% in the TRX-II group (p < 0.01) from the control value of 75%. SOD and catalase reduced the incidence of VF to 43 and 33%, respectively (NS). During the entire reperfusion period, the incidence of VF in the SOD group was 79%, as compared to 83% in the control group. In the catalase and TRX-II groups, the incidence of VF was significantly reduced to 42 and 25%, respectively. These findings indicate that SOD failed to protect against the reperfusion-induced arrhythmias. h-Thioredoxin exerted a protective effect against these arrhythmias; a concentration of approximately 0.1 micro was the most effective.

Animals↗
PubMed1995

Cellular levels of thioredoxin associated with drug sensitivity to cisplatin, mitomycin C, doxorubicin, and etoposide.

Thioredoxin, a cellular thiol, functions as a self-defense mechanism in response to environmental stimuli, including oxidative stress. We first determined cellular levels of thioredoxin in several human bladder and prostatic cancer cell lines resistant to cis-diamminedichloroplatinum(II) (cisplatin). All cisplatin-resistant cell lines had much higher levels of thioredoxin than those in their drug-sensitive parental counterpart. We then, by introducing thioredoxin antisense expression plasmids into human bladder cancer T24 cells, established two bladder cancer cell lines that had decreased levels of thioredoxin. These thioredoxin antisense transfectants showed increased sensitivity to cisplatin and also to other superoxide-generating agents, i.e., doxorubicin, mitomycin C, etoposide, and hydrogen peroxide, as well as to UV irradiation, but not to the tubulin-targeting agents, vincristine, and colchicine. Cellular levels of thioredoxin thus appear to limit sensitivity to various superoxide-generating anticancer drugs in cancer cells.

Antineoplastic Agents↗
PubMed1995

Role of ADF/TRX and its inhibitor on the release of major basic protein from human eosinophils.

Adult T cell leukemia-derived factor (ADF)/Thioredoxin (TRX), originally defined as an IL-2 receptor alpha-chain/p55 inducer, has many cytokine-like activities. We reported that the release of major basic protein (MBP) from mature eosinophils stimulated with cytochalasin B and C5a were augmented after preincubation with recombinant ADF/TRX. The addition of a TRX specific inhibitor, BE40644, suppressed the augmentation of MBP release from mature eosinophils. It is suggested that BE40644 is applicable in allergic diseases associated with eosinophils.

Benzoquinones↗
PubMed1995

Thiol-mediated redox regulation of apoptosis. Possible roles of cellular thiols other than glutathione in T cell apoptosis.

Thiol redox status modulates various aspects of cellular function. We demonstrate that oxidation of cellular sulfhydryl (SH) groups induces apoptosis. In Jurkat T cells and human PBL blasts, the fraction of apoptotic nuclei increased after treatment with an SH-specific oxidant, diamide. Analysis of DNA fragmentation and nuclear morphology also indicated that SH oxidation could induce apoptosis. In the apoptosis induced by SH oxidation, the decrease of cellular glutathione was transient and the increase of glutathione disulfide was observed only after apoptotic changes had occurred. Depletion of cellular glutathione with buthionine sulfoximine failed to induce apoptosis, despite a marked decrease of cellular glutathione, which was greater than that observed in apoptosis induced by diamide. Thus, the changes of cellular glutathione or glutathione disulfide may not be the major cause of apoptosis induced by diamide. Intracellular adult T cell leukemia-derived factor/human thioredoxin, another thiol-related antioxidant protein, was oxidized by incubation with diamide. These results suggest that thiol redox status is one of the key factors of the apoptotic pathway in which thiols other than glutathione may play even more critical roles.

Apoptosis↗
PubMed1995

Upstream mechanisms of glycogen synthase activation by insulin and insulin-like growth factor-I. Glycogen synthase activation is antagonized by wortmannin or LY294002 but not by rapamycin or by inhibiting p21ras.

This study was undertaken to define intracellular signaling pathways upstream to glycogen synthase activation. First, we examined the role of the two pathways of insulin signaling, Ras-dependent and wortmannin/LY294002-sensitive, in glycogen synthase activation. Although negative dominant Ras (Ras17N) induction in PC12 cells markedly decreased activities of mitogen-activated protein kinase (MAP) and pp90 S6 kinase in response to insulin or insulin-like growth factor I (IGF-I), activation of glycogen synthase by these agents was unaffected by negative dominant Ras induction. In contrast, wortmannin and 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), inhibitors of phosphatidylinositol 3-kinase, antagonized glycogen synthase activation in response to insulin or IGF-I. Next, we examined the contribution of pp70 S6 kinase, one of the wortmannin/LY294002-sensitive signaling molecules on glycogen synthase activation. Immunosuppressant rapamycin completely blocked activation of pp70 S6 kinase by insulin or IGF-I, but rapamycin alone or in combination with induction of negative dominant Ras failed to antagonize glycogen synthase activation by these hormones. These data suggest that 1) activation of Ras-MAP kinase is not necessary for stimulation of glycogen synthase and 2) activation of wortmannin/LY294002-sensitive pathway, independent of pp70 S6 kinase, plays a key role in glycogen synthase regulation in PC12 cells.

Amino Acid Sequence↗
PubMed1995

Structure of the mouse thioredoxin-encoding gene and its processed pseudogene.

Thioredoxins (TXN) are small proteins with various biological functions, such as redox regulation, found in many species including bacteria, plants and animals. We previously reported the isolation of the TXN-encoding cDNAs from human and mouse. In order to elucidate the functions of the mammalian TXN system, we planned to generate Txn knockout mice, and cloned the genomic DNA fragments using the Txn cDNA as a probe. The Txn gene extends over 12 kb and consists of five exons separated by four introns. Detailed Southern analyses revealed that the mouse genome contains only one active Txn gene and one processed pseudogene (Txn-ps1), in contrast to some species which have families of active TXN-encoding genes. These findings should help to understand Txn itself, and provide a basis for transgenic experiments by gene targeting.

Amino Acid Sequence↗
PubMed1995

Persistent oxidative stress in cancer.

DNA of cancers such as renal cell carcinoma and mammary invasive ductal carcinoma, is persistently exposed to more oxidative stress than that of adjacent normal tissue. We suggest that the concept of 'persistent oxidative stress in cancer' may open up a new research area, explaining part of the characteristic tumor biology of cancer such as activated transcription factors and proto-oncogenes, genomic instability, chemotherapy-resistance, invasion and metastasis.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1995

Expression of the adult T-cell leukemia-derived factor, human thioredoxin, in the allotransplanted canine lung.

The relationship between the expression of adult T-cell leukemia-derived factor, human thioredoxin (ADF/TRX), and rejection in transplanted canine lungs was investigated in this study. Of a total 27 adult mongrel dogs, 24 underwent allotransplantation of the left lung with no immunosuppressant and the other three underwent autotransplantation of the left lung. Of the allotransplanted dogs, five were killed on postoperative day (POD) 1, five on POD 2, seven on POD 3, and seven on POD 5, while all three autotransplanted dogs were killed on POD 5. Histological examination was performed on the 24 allotransplanted left lungs (group A), 12 autologous right lungs (group B), and bilateral lungs of the three autotransplanted dogs (group C). The lung tissue was stained with anti-ADF antibody, and the high-ADF-producing cells (ADFh cells) in a randomly chosen field were counted as an index of ADF expression. As the signs of rejection in the group A lungs became more severe with time, the ADFh cells increased in number: 1.68 +/- 1.15, 6.08 +/- 3.44, 14.03 +/- 6.09, and 47.74 +/- 18.89, on PODs 1, 2, 3, and 5, respectively. However, the number of ADFh cells in the group B and group C lungs did not become significantly different from that on POD 1 in group A. These results suggested that ADF/TRX expression may be useful for the early diagnosis of rejection of transplanted lungs.

Animals↗
PubMed1995

Identification of novel CD23 transcripts on human T and B lymphocytes and eosinophil cell line.

The main aim of the present studies was to investigate the structure of the human low-affinity IgE Fc receptor (CD23) present on T and B lymphoid cells and eosinophil cell line. A novel finding in these studies has been the detection and sequence analysis of CD23 transcripts in human T lymphocytes. These studies have established that some of the human T-cell populations analyzed express CD23 mRNA and that its structure is quite similar to that previously described for human B lymphocytes. A second major finding in these studies is that some human T- and B-cell lines and eosinophil cell line contain multiple forms of CD23 transcripts. These appear to be generated via alternative splicing, resulting in transcripts that may encode a truncated, possibly secretory form of CD23. These findings in human T and B lymphocytes and eosinophils provide new information about the structure of lymphocyte CD23 and suggest that alternative processing of transcripts generates CD23 mRNA that encodes CD23 isoforms. These studies are the first experimental evidence showing that CD23 isoforms may occur in the human and are the first direct evidence for production of CD23 by human T lymphocytes. In addition, these studies provide the first experimental evidence that T and B lymphocytes express CD23 transcripts lacking exon 3-encoded sequences, raising the possibility that a secretory form of CD23 may be synthesized by human T and B lymphocytes, and eosinophils.

Amino Acid Sequence↗
PubMed1995

Induction of ADF/TRX by oxidative stress in keratinocytes and lymphoid cells.

Adult T-cell leukemia-derived factor (ADF)/human thioredoxin (TRX) has thiol-dependent reducing activities and is known to have regulatory roles on the DNA-protein interaction and cell activation. Inducive effect of ultraviolet (UV) has been indicated because of the enhanced expression of ADF/TRX in epidermal cells of sun-exposed skin, as determined by immunohistochemical staining with antibody against recombinant ADF (rADF). We studied the effect of UVB irradiation and other oxidative stress on the expression of ADF/TRX in epithelial cells as well as lymphoid cells, as HTLV-1 and Epstein-Barr virus-transformed lymphoid cells constitutively produce ADF/TRX. Using immunohistochemical staining anti-ADF antibody, the enhancement of ADF/TRX expression on primary culture of human keratinocytes was demonstrated, 12 h after 20 mJ/cm2 UVB irradiation. Western blot analysis of the ADF/TRX protein in the cell lysates also showed the significant induction. In in situ hybridization, induction of ADF/TRX mRNA was detected after 4 h of UV exposure. ADF/TRX was also induced in a HTLV-1 (+) T-cell line, MT-1, by UVB or H2O2 dose dependently. The augmentation of ADF/TRX was observed 6 h after treatment of H2O2.

Blotting, Western↗
PubMed1995

Expression of adult T-cell leukemia-derived factor in bronchoalveolar lavage cells after canine lung transplantation.

Lung transplantation is now an accepted therapeutic option for patients with end-stage lung disease, and an early diagnosis of rejection is essential in the management of these patients. Adult T-cell leukemia-derived factor (ADF), known as a human homolog of thioredoxin, has been shown to be induced by a variety of stresses. In this study we examined ADF expression in lung tissues and bronchoalveolar lavage cells after canine lung transplantation to determine whether it could be induced by allogenic stimulations and could be used to diagnose early rejection. Allotransplantations were performed in adult mongrel dogs, and immunosuppression was performed from the day of operation to the fifth postoperative day. No immunosuppressant was given from the sixth to the tenth postoperative days. Animals were put to death on the tenth postoperative day. Bronchoalveolar lavage was performed on the fifth and tenth postoperative days, and the lavage cells and lung tissues were examined immunohistochemically with anti-ADF antibody. The grades of rejection were as follows: grade 1 in two animals, grade 2 in three animals, and grade 3 in two animals. The percentages of ADF high-producer cells in bronchoalveolar lavage cells on the fifth and tenth postoperative days were 4.29% +/- 2.65% and 26.6% +/- 3.99%, respectively (p < 0.01). The percentages of ADF high-producer cells in normal healthy dogs and in those with grade 1, grade 2, and grade 3 rejection were 3.00% +/- 1.64%, 20.5% +/- 9.00%, 25.5% +/- 6.06%, and 34.5% +/- 6.50%, respectively. The percentage in each rejection group was significantly higher than that in normal healthy dogs (p < 0.05). These results suggest that examination of bronchoalveolar lavage cells with ADF staining may be useful in the early diagnosis of rejection.

Animals↗
PubMed1995

Biochemical and topological analysis of adult T-cell leukaemia-derived factor, homologous to thioredoxin, in the pregnant human uterus.

Adult T-cell leukaemia-derived factor (ADF), homologous to thioredoxin, displays various biological activities, such as radical scavenging action and the reduction of protein disulphide bonds. We examined the biochemical and immunohistochemical localization of ADF in the pregnant human uterus, using two heteroantibodies to ADF, antibody C and W. Immunohistochemically, decidua and trophoblast cells were intensely stained by antibody C. The concentration of ADF-like substance in the decidua was 95.9 ng/mg protein, determined by enzyme-linked immunosorbent assay. The molecular weight of ADF-like substance in these tissues was determined by gel electrophoresis to be 13 kDa, the same as that of recombinant ADF. These findings indicate that abundant ADF is present in decidua and trophoblast cells; the localization of such a potent dithiol reducing substance may be beneficial in protecting the fertilized egg and placental trophoblasts from the cytotoxic effects of oxygen radicals.

Adult↗
PubMed1995

TNF-alpha regulates IL-4-induced Fc epsilon RII/CD23 gene expression and soluble Fc epsilon RII release by human monocytes.

We examined the regulatory effects of TNF-alpha on IL-4-induced gene expression of the low-affinity receptor for IgE (Fc epsilon RII/CD23) in human monocytes and IL-4-induced soluble Fc epsilon RII (sFc epsilon RII) release from monocytes. IL-4-induced Fc epsilon RII expression on the surface of monocytes was reduced by TNF-alpha as early as 1 day after culture and the effect of TNF-alpha increased with prolonged culture. The present analysis was designed to examine whether or not TNF-alpha could suppress IL-4-induced Fc epsilon RII mRNA expression and enhanced IL-4-induced sFc epsilon RII release. The addition of TNF-alpha to monocyte cultures with IL-4 significantly reduced Fc epsilon RII expression on the surface of monocytes and significantly increased sFc epsilon RII release from monocytes. Over time, there was an inverse relationship between the disappearance of cell surface Fc epsilon RII and the appearance of sFc epsilon RII in culture supernatants. Fc epsilon RII mRNA expression in monocytes cultured with IL-4 was not affected by TNF-alpha when examined at 6 h after cultivation. When the cells were cultured with TNF-alpha for more than 24 h, however, TNF-alpha down-regulated IL-4-induced Fc epsilon RII mRNA levels. This correlated with the kinetics of down-regulation of IL-4-induced Fc epsilon RII expression on the surface of monocytes by TNF-alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗